Multiscale modelling of claudin-based assemblies: A magnifying glass for novel structures of biological interfaces

Claudin-10b cation channels in tight junction strands: Octameric-interlocked pore barrels constitute paracellular channels with low water permeability

“…The models differ regarding the claudins investigated, the input of (structural and functional) in vitro/in situ data and the in silico methodology on which they are based. The joined double rows (JDR) model of CLDN15 suggested by Suzuki et al [14] is, after several extensive refinements [23] , [24] , [25] , [28] and extension to other classic claudins [15] , [26] , [41] , [53] , the one that is supported most by experimental and modeling data [10] . However, the validity of the model, especially in detail is unclear.…”

“…Different models of the claudin backbone of TJ strands with embedded paracellular channels have been reported [10] , [14] , [15] , [18] , [19] , [20] , [21] , [22] , [23] , [41] . The models differ regarding the claudins investigated, the input of (structural and functional) in vitro/in situ data and the in silico methodology on which they are based.…”

“…Based on Suzuki’s CLDN15 model, a β-barrel-like tetrameric pore scaffold has been widely assumed for channel-forming claudins [14] , [15] , [24] , [53] , although alternative tetrameric pore structures have been suggested, too [21] , [23] , [53] . The oligomeric channels have to be stringed together to form the polymeric backbone of TJ strands.…”

“…The molecular mechanism of claudin oligo/polymerization resulting in strand and channel formation is largely unclear. Different architectural models have been suggested for CLDN15 and other classic claudins [10] , [14] , [15] , [18] , [19] , [20] , [21] , [22] , [23] . The joined double rows (JDR) model of CLDN15 suggested by Suzuki et al [14] , refined [24] , [25] and expanded to other classic claudins based on sequence homology [15] , [26] , is the one that is supported most by experimental and modeling data [10] .…”

The Impact of Pathogenic and Artificial Mutations on Claudin-5 Selectivity from Molecular Dynamics Simulations

“…The blood-brain barrier (BBB) is a highly selective interface that separates the capillary blood flow from the brain parenchyma, and it is composed of brain endothelium, pericytes and astrocytes. Brain endothlial cells are tightly bound at their lateral membranes by multimeric protein complexes named tight junctions (TJs) (1–3), that are quite impermeable to solutes. TJ proteins are organized in continuous networks of transmembrane strands, and are responsible for strictly regulating the diffusion of solutes through the intercellular space between cells, named the paracellular space.…”